Experimental autoimmune encephalomyelitis (EAE) involves a pathological process which causes CNS inflammatory lesions, demyelination, and overt clinical signs. The chronic or relapsing form of EAE mimics in many ways the human disease, multiple sclerosis. Many of the processes which have been studied in EAE may have direct application to eventual therapies and prophylaxis in MS and other human demyelinating diseases. The overall goal of this proposal is to describe mechanisms which regulate the activity of encephalitogenic T lymphocyte lines. The BP-1 T lymphocyte line has been selected for its ability to recognize and respond to myelin basic protein. The BP-1 line acquired the capability to induce clinical EAE and DTH reactions to BP in recipient rats only after activation with BP presented by histocompatible accessory cells. Furthermore, injection of irradiated, activated BP-1 cells induced resistance to active EAE produced by injection of BP in CFA. The maturation from resting to fully activated T effector cells thus represents a crucial stage in the development of clinical EAE as well as protection against EAE. Aim 1) To evaluate the ability of accessory cells from thymus, spleen, lymph nodes, peritoneum, and brain capillary endothelium to activate encephalitogenic T lymphocytes, and to characterize the activation sequence. Aim 2) To determine if immunologic recognition of activated BP- 1 cells is associated with protection against actively induced EAE. This proposal will study the interactions between the T cells that mediate EAE and the antigen presenting cells which control the activation and migration of the T cells into the tissue. This interaction may be critical in the maintenance of nonresponse to self as well as the inflammation which results in EAE. Thus, information from this research may contribute significantly to the regulation of inflammatory processes in the CNS and perhaps in other tissues as well.